This discovery relates to methods and apparatus useful for the selective and quantitative detection of N-nitrosamines in samples containing other nitrogen compounds. Specifically, this discovery relates to improved electrolytic conductivity detector systems and methods capable of selectively and quantitatively detecting N-nitrosamines.
There are several classes of nitroso derivatives but those which have become of the most significant interest are the N-nitrosamines. These are secondary amines having a nitrosyl radical connected to a nitrogen resulting in a basic N-nitrosamine configuration of ON--N.sup..dbd..
The interest in detecting N-nitrosamines has been stimulated by evidence which suggests these compounds may be carcinogenic to humans. At the present time, however, there exist few known methods for the quantitative detection of N-nitroso compounds.
One method which is suggested in an article entitled "Gas Chromatography and Selective Detection of N-Nitrosamines" by John W. Rhoades and Donald E. Johnson which appeared in the October, 1970 issue of Journal of Chromatographic Science, Vol. 8, page 616. In that article it is stated that the selective detection of amines and N-nitrosamines in neutral extracts of cigarette tars can be undertaken by the pyrolysis of N-nitrosamines after GC separation. The article further states that a Coulson liquid conductivity detector from Tracor, Inc. was used and that instead of hydrogenating samples in the presence of a nickel catalyst contained in a quartz tube at temperatures of about 850.degree. C., a pyrolysis reaction was obtained by using an empty quartz tube at temperatures in the range of 400.degree.-600.degree. C.
It is not clear, however, whether the pyrolysis took place in the presence of hydrogen but it is specified in the article that ammonia was obtained as the degradation product of many amines and N-nitrosamines. Because of this, it would appear that the method could not be used for the accurate selective detection of N-nitrosamines.
Another method for the quantitative detection of N-nitrosamines is called the Thermal Energy Analyzer (TEA). Two articles describing testing which has been accomplished with the TEA method are:
Fine, D. H. et al, "Description of the Thermal Energy Analyzer (TEA) for Trace Determination of Volatile and Nonvolatile N-nitroso Compounds", Analytical Chemistry, Vol. 47, No. 7, page 1188 (1975).
Krull, I. S. et al "Thermal Energy Analysis for N-nitroso Compounds" American Laboratory, Vol. 11, No. 5, page 84 (May 1979).
The TEA method of nitrosamine detection involves the catalytic clevage of the nitrosyl radical from the nitroso compound. The products from the catalytic reaction are then sent through a cold trap which is designed to condense most organic materials and to allow the nitrosyl radical to move through the trap in a gaseous state. The nitrosyl radical is then directed to a stainless steel reaction chamber where it is reacted with ozone to form an electronically excited nitrogen dioxide. The light which is emitted from the nitrogen dioxide is detected by a sensitive photo multiplier and this measurement is then used to determine the quantity of N-nitroso compounds.
It appears that the TEA method can be used together with gas chromatographs or a high performance liquid chromatographs. The TEA detectors are manufactured by Thermo Electron Corporation of Waltham, Mass.
Other devices have been used for the quantitative detection of nitrogen compounds. The Hall electrolytic conductivity detector, for example, is a device which has been used as a specific detector for gas chromatography. The Hall type detector is disclosed in U.S. Pat. Nos. 4,032,296 and 3,934,193 which are incorporated herein by reference. Also, a Hall electrolytic conductivity detector has been sold by Tracor Instruments for several years.
Very basically, a Hall electrolytic conductivity detector (HECD) system includes a gas chromatograph coupled to a reactor which in turn is coupled to a differential conductivity cell. The Hall detector has three modes of operation. The first is in a halogen or chlorine detection mode. In that mode, chlorine is transformed to hydrochloric acid (HCl) and a conductivity response of ionizable HCl in a solvent-type medium is measured in the differential conductivity cell. This particular mode of operation is not pertinent to the present invention.
Another mode of operation, not pertinent to the invention, is the sulphur mode for the detection of sulfur compounds. In this mode, the sulfur is catalytically changed to SO.sub.2 in the reactor. The SO.sub.2 is then mixed with an electrolyte or solvent and the conductivity change in the electrolyte is measured.
The mode of detection which is most relevant to this invention is the nitrogen mode. In that mode various nitrogen compounds such as amines, carbamides, ureas, triazines and the like are reduced with nitrogen in the presence of a nickel catalyst to form quantitatively determinable amounts of ammonia. The ammonia is then mixed with a suitable solvent and the conductivity change of the solvent is measured in an electrolytic conductivity cell.
Typically, in the nitrogen mode, the HECD reactor is operated at a very high temperature of from 800 to 900 degrees C. Hydrogen as a reaction gas is fed into the nickel reaction chamber with the eluate from the chromatographic column.
The difficulty with the nitrogen mode of operation is that it is broadly applicable to a number of nitrogen compounds and therefore is not specific to nitrosamines. Any other related nitrogen compounds which might have elution times close to the desired nitrosamines will provide interfering signals which mask and prevent an effective measure of the quantitative amounts of nitrosamines present.